Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease

Abstract

The major pathology in Parkinson's disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation of microglial cells. The objective of this study is to determine the effect and mechanism of miR-132-3p in regulating neuroinflammation and the degeneration of dopaminergic neuron in PD.The expressions of miR-132-3p in brain tissues of PD patients, LPS induced BV-2 cells and MPTP induced PD mouse models were detected. The effect of miR-132-3p and GLRX in cell viability, apoptosis and inflammation was verified in BV-2 cells.The activation of Iba1 in substantia nigra pars compacta and the loss of tyrosine hydroxylase were detected in PD mouse models and the mobility of mouse models was assessed as well. The targeting relationship between miR-132-3p and GLRX was confirmed by RIP and dual luciferase reporter gene assay. Elevated expression of miR-132-3p and decreased expression of GLRX were found in PD patients and cells models. Overexpression of miR-132-3p can induce activation of microglial cells, which can be reversed by GLRX overexpression. Collected evidence in both cell model and mouse models showed the effect of miR-132-3p in enhancing the activation of microglial cells and the loss of microglia cells, which was achieved by mediating GLRX.

lncRNA NEAT1 promotes autophagy of neurons in mice by impairing miR-107-5p

“…This section of the experiment co-transfected NEAT1-Wt/NEAT1-Mut with miR-107-5p mimics negative control and miR-107-5p mimics into SH-SY5Y cells in respective. The luciferase activity was subsequently determined by measuring the fluorescence intensity by using the Dual-Luciferase System (Promega, USA) [ 14 ].…”

Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases

“…Dysregulation of miRNA expression profiles has been described in several brain areas and fluids of PD patients, as well as in iPSCs-derived DNs generated from affected patients. Table 2 shows a list of 15 miRNAs (let-7b, miR-34b, miR-124, miR-126, miR-132, miR-133b, miR-144, miR-148b, miR-184, miR-199a, miR-204, miR-218, miR-221, miR-338, miR-425) that were found dysregulated by at least two independent studies in nervous tissues (midbrain, prefrontal cortex, amygdala, laser-micro dissected DNs, or anterior cingulate gyrus) [ 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ], iPSC-derived DNs [ 119 ] and circulating fluids (CSF, plasma, serum, peripheral blood) [ 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ] of PD patients, thus supporting their potential utility as biomarkers and/or therapeutic targets.…”

“…MiR-132 was also proposed as a good candidate for monitoring PD progression as well as response to various therapeutic approaches [ 125 , 143 , 152 ] ( Table 2 ). Upregulation of this miRNA was associated with neuroinflammation, microglial activation, and DNs neurodegeneration [ 117 , 148 ] ( Table 2 , Figure 2 ).…”

Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs

“…miR-132-3p-induced activation of microglia cells can be reversed by GLRX overexpression. Suppression of miR-132-3p alleviates neuroinflammation and dopaminergic neurodegeneration in PD mouse models [ 93 ].…”